PM2.5 constituents are tightly linked to the initiation of many cardiovascular diseases (CVDs). Little is known, however, about the events which critical components of PM2.5 can induce the initiating events in CVDs. C57BL/6 female mice were exposed to PM2.5 (3 mg/kg b.w.) from four different cities (Taiyuan, Beijing, Hangzhou, and Guangzhou) by oropharyngeal aspiration every other day. PM2.5 from Taiyuan increased the diastolic function of the hearts and induced myocardial fibrosis with increased areas of interstitial fibrosis through the NOX4/TGF-β1/Smad 3/Col1a1 pathways. Pb, Cr, Mn, Zn, and most of the polycyclic aromatic hydrocarbons (PAHs) were positively associated with the related indicators of cardiac diastolic function and myocardial fibrosis by using Pearson correlation (R2 = 0.9085-0.9897). To determine the critical components in PM2.5 that can induce the occurrence of myocardial fibrosis, BEAS-2b cells were treated with one or more of five candidate components with/without Guangzhou PM2.5, and then the conditioned medium of BEAS-2b was used to culture AC16 cells. The results showed that Zn + Pb + Mn + BaP with PM2.5 from Guangzhou exposure significantly increased reactive oxygen species production of BEAS-2b cells and induced a dramatic increase of myocardial fiber-related gene expression (Col1a1 and TGF-β) in AC16 cells. It indicated that the different mass concentrations of Zn, Pb, Mn, and ΣPAHs in PM2.5 might be the critical factors that modulated myocardial fibrosis induction by targeted. Our study provided a novel avenue for further elucidation of molecular mechanisms of PM2.5 components-induced myocardial fibrosis.
Keywords: CVD; Critical components; Myocardial fibrosis; PM(2.5); Synergy cytotoxicity.
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